During the past two years we have shown that gastrin is a trophic hormone for gastric and duodenal mucosa. Cultures of gastric and duodenal mucosal cells have been maintained in vitro for up to 6 months and have been shown to be dependent on gastrin. We propose to continue this study by examining the role of the gastrointestinal hormones as regulators of growth and differentiation. (1) The degree of differentiation of cells cultured from gastric and duodenal mucosa will be examined and effects of gastrin on that differentiation elucidated. (2) The effects of secretin and CCK on protein, DNA and RNA synthesis will be studied in whole animals and tissue and organ cultures of gastric and duodenal mucosa. (3) The mechanism by which gastrin increases protein synthesis will be examined by measuring changes in time of RNA and DNA synthesis in response to gastrin and correlating them with protein synthesis using organ cultures of gastric and duodenal mucosa. The effect of inhibitors of various parts of the protein synthetic machinery will also be examined. (4) The identity of the proteins whose synthesis is stimulated by gastrin will be studied using radioautography, disaccharidase and pepsin assays, and glycoprotein determination. (5) Mucosal tissue from patients with gastric ulcer, pernicious anemia, atrophic gastritis, or cancer will be cultured and its growth characteristics compared with normal tissue. The effects of G.I. hormones on the growth of this tissue will also be described. (6) We will study the mechanism whereby gastrin and CCK inhibit intestinal absorption by examining uni-directional fluxes of Na and water. The overall objective of this work is to determine the role of the gastrointestinal hormones in the regulation of growth and differentiation of normal and abnormal gastric and duodenal mucosa.